Biomarker for Aggressive Prostate Cancer Found

Men whose serum calcium levels fall within the high end of the normal range are three times more likely to develop fatal prostate cancer, says a report in the journal Cancer Epidemiology, Biomarkers & Prevention.

The results suggest the possibility of a new biomarker for aggressive prostate cancer, the researchers say.

But one expert cautions against reading too much into the study, given the relatively small number of individuals involved.

Researchers used data from the National Health and Nutrition Examination Survey (NHANES) and NHANES Epidemiologic Follow-up Study to determine the risk of prostate cancer among men with relatively high, but still normal, blood serum calcium readings.

Early High Levels, Later Prostate Worries
Gary Schwartz, Ph.D., of Wake Forest University Health Sciences, and Halcyon Skinner, Ph.D., of the University of Wisconsin, Madison, conducted the study.

Participants represented a random cross-section of American households, and they were first examined in the early 1970s. At that time, blood samples were drawn, and serum calcium levels obtained.

The participants were then monitored for an average of almost 10 years. Drs. Skinner and Schwartz wondered if, in this population, there was any correlation between baseline serum calcium and risk of prostate cancer later in life.

"It would be the equivalent of a high school guidance counselor looking at SAT scores from students 20 years ago to see how [the scores] predict academic or business success," Dr. Schwartz explains.

In the study, 2,814 men between the ages of 24 and 77 at the time of their initial blood draw were included in the analysis, yielding 85 total cases and 25 fatal cases of prostate cancer over 46,188 person-years of follow-up.

When researchers looked at individuals' serum calcium levels, the authors found that those whose serum calcium readings during the initial blood draw fell at the highest-third of the normal range (between 9.9 milligrams per deciliter [mg/dL] and 10.5 mg/dL) were about 2.7 times more likely to die of prostate cancer than those with readings in the lowest or middle thirds (between 9.0 mg/dL and 9.8 mg/dL).

That association held even adjusting for the most well-known prostate cancer risk factors - age, weight, race, and family history.

In contrast, no relationship was observed between serum calcium levels and "incident" prostate cancer - that is, with the occurrence of new cases of prostate tumors in general.

Dr. Durado Brooks, director of prostate and colorectal cancer at the American Cancer Society says, "There's been a lot of work around dietary calcium - calcium supplements - and prostate cancer risk, but I haven't seen much looking at serum calcium levels and prostate cancer risk, so I think it's an interesting angle to take on this issue."

Though he cautions against "making too much about this," given the small number of affected individuals in the study, Dr. Brooks says the research should nevertheless "stimulate additional work in this area."

Serum calcium levels have almost nothing to do with dietary calcium intake, Dr. Schwartz emphasizes. Serum calcium levels are tightly regulated and are characteristic of an individual in the same way as body temperature and height.

Thus, whether an individual eats a diet rich in cheese and milk or not, serum calcium levels generally do not vary by more than about 2 percent; instead, people are probably genetically predisposed to have one level or another, says Dr. Schwartz.

If Repeated, a Very Significant Finding
The real "eye-opener," Dr. Brooks notes, is that, should the results be validated in other studies, serum calcium would represent one of the most significant known risk factors for prostate cancer, and the only one that could be clinically modified.

"The relative risk of prostate cancer for being black is about two, and the relative risk for having a positive family history is about 2.5,” he says. “So a relative risk greater than 2.5 is actually bigger than anything we know. But what makes this really interesting is, if this is causal, it can be changed with medicine."

First, though, the results must be validated in other studies, says Dr. Brooks.

Researchers must then determine whether calcium itself actually causes this increased risk or is merely a marker of some other biological process. Either way, should the data be borne out, Dr. Brooks suggests another possible use of serum calcium.

Given that most cases of prostate cancer never become aggressive, he says, "Maybe we could use those values to guide medical treatment, to decide who needs more aggressive therapy. It could be one factor in helping make a treatment decision."

Always consult your physician for more information.

Online Resources

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American Cancer Society

Cancer Epidemiology, Biomarkers & Prevention - Serum Calcium and Incident and Fatal Prostate Cancer in the National Health and Nutrition Examination Survey

National Cancer Institute (NCI)

National Prostate Cancer Coalition

NIH - Prostate Cancer

Prostate Cancer Foundation